Nobiletin and tangeretin, which are polymethoxyflavonoids, are citrus fruit-specific flavonoids, and in recent years, the compounds have been found to have a variety of physiological activities such as cancer-preventive, senescence-retarding, and anti-atherogenic activities. In addition, it has been reported that nobiletin has an Alzheimer's-improving activity (see Non Patent Literature 1) and a neurite elongation activity (see Patent Literature 1).
On the other hand, all the studies on the physiological activities of nobiletin and tangeretin have been made for nobiletin and tangeretin per se (unchanged compounds), but recent reports show that the compounds are absorbed from the intestinal mucosa and metabolized into some demethylated compounds, and 6 methoxy groups in all are partially demethylated (see Non Patent Literature 2).
An example of a study on a cancer-suppressing activity of nobiletin using the following synthesized demethylated compounds shows that with respect to the effect of preventing development of cancer by suppressing synthesis of nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), wherein NO, iNOS and COX-2 promote inflammation and development of cancer, three kinds of demethylated demethylnobiletins (in particular, 3′-demethylnobiletin, 4′-demethylnobiletin, and 3′,4′-didemethylnobiletin) each have a drastically higher effect than nobiletin per se. In particular, 4′-demethylnobiletin has a high activity (see Non Patent Literature 3).
A study on the physiological activities of two kinds of polymethoxyflavonoids (in particular, 5-hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone and 3′-hydroxy-5,6,7-trimethoxyflavone) having a hydroxyl group at position 5 or 3′ and obtained from an orange as polymethoxyflavonoids which are present in a citrus fruit and have a hydroxyl group also show that the compounds suppress strongly expression of mRNA of iNOS and COX-2 and induce apoptosis of breast cancer cells.
Both the studies suggest that the physiological functions of polymethoxyflavonoids are significantly enhanced by substituting part of the methoxy groups with hydroxyl groups, and the demethyl polymethoxyflavonoids are expected to be used as functional components.
However, the contents of such polymethoxyflavonoids which are contained in any currently known natural substance and in which part of methoxy groups have been substituted by hydroxyl groups are very low, and hence it is not realistic to extract and use the component using these substances as raw materials.